Cytokine Production Is Differentially Modulated in Malignant and Non-malignant Tissues in ST2-Receptor Deficient Mice

IL-33/ST2 axis has been shown to exert both pro- and anti- effects in wound healing and tumor development. To further understand the role of this cytokine complex, we characterized comparatively the inflammatory component of a malignant tissue and non-malignant tissue in mice lacking ST2 receptor (S...

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Bibliographic Details
Published in:Inflammation 2018-12, Vol.41 (6), p.2041-2051
Main Authors: Viana, Celso Tarso Rodrigues, Orellano, Laura Alejandra Ariza, Pereira, Luciana Xavier, de Almeida, Simone Aparecida, Couto, Letícia Chinait, de Lazari, Marcela Guimarães Takahashi, Andrade, Silvia Passos, Campos, Paula Peixoto
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - metabolism
Cell number
Clonal deletion
Cytokines
Cytokines - biosynthesis
Gene Expression Regulation, Neoplastic
Immunology
Inflammation
Interleukin-1 Receptor-Like 1 Protein - deficiency
Interleukin-33
Internal Medicine
Mammary gland
Mice
Mice, Knockout
Monocyte chemoattractant protein 1
Neoplasms - metabolism
Original Article
Pathology
Pharmacology/Toxicology
Polyurethane
Rheumatology
Rodents
Transforming growth factor-b1
Tumor necrosis factor-α
Tumors
Wound healing
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Summary:IL-33/ST2 axis has been shown to exert both pro- and anti- effects in wound healing and tumor development. To further understand the role of this cytokine complex, we characterized comparatively the inflammatory component of a malignant tissue and non-malignant tissue in mice lacking ST2 receptor (ST2-KO). KO mice and their wild-type (WT) counterparts were either implanted subcutaneously with polyether-polyurethane sponge discs to induce non-malignant fibrovascular tissue growth or inoculated with 4T1 cells to induce mammary tumor. Loss of ST2 receptor in mice resulted in enhanced mammary tumor and fibrovascular tissue relative to the WT animals. The inflammatory parameters (MPO and NAG activities, levels of the cytokines CXCL1/KC, CCL2, TNF-α, TGF-β1, and mast cell number) were differentially modulated in both tissues. In tumors, these parameters were, overall, lower compared with those in tumors of WT mice. In KO implants, CXCL1/KC and TNF-α levels increased; MPO, NAG, and CCL2 levels decreased relative to the WT implants. In addition, deletion of ST2 receptor inhibited mast cell recruitment but had no effect on TGF-β1 levels in implants. Our study has shown antitumorigenic effect of ST2 in mammary tumor and this may be mediated by downregulation of pro-inflammatory cytokines (CXCL1/KC, CCL2, TNF-α, and TGF-β1). Conversely, in the fibrovascular tissue, lack of ST2 receptor resulted in differential modulation of cytokine production. Differential signaling mechanisms may be activated by IL-33/ST2 axis to modulate cytokine production in malignant and non-malignant proliferative processes.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-018-0847-y